• Kate Leslie, Paul S Myles, Jessica Kasza, Andrew Forbes, Philip J Peyton, Matthew T V Chan, Michael J Paech, Daniel I Sessler, W Scott Beattie, P J Devereaux, and Sophie Wallace.
• From the Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, and Anaesthesia, Perioperative and Pain Medicine Unit, and Department of Pharmacology and Therapeutics, University of Melbourne, and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (K.L.); Department of Anaesthesia and Perioperative Medicine, The Alfred Hospital, and Academic Board of Anaesthesia and Perioperative Medicine, and Department of Epidemiology and Preventive Medicine, Monash University, and National Health and Medical Research Council Practitioner Fellow, Melbourne, Australia (P.S.M.); Department of Epidemiology and Preventive Medicine (J.K., A.F.), Monash University, Melbourne, Australia; Department of Anaesthesia, Austin Hospital, and Department of Surgery, University of Melbourne, Melbourne, Australia (P.J.P.); Department of Anaesthesia, Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China (M.T.V.C.); Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Australia, and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (M.J.P.); Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio (D.I.S.); Department of Anesthesia, University of Toronto, and Department of Anaesthesia, Toronto General Hospital, Toronto, Ontario, Canada (W.S.B.); Population Health Research Institute, Hamilton Health Sciences and McMaster University, and Departments of Medicine, Clinical Epidemiology, and Biostatistics, McMaster University, Hamilton, Ontario, Canada (P.J.D.); and Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (S.W.).
• Anesthesiology. 2015 Dec 1; 123 (6): 1267-80.

BackgroundThe Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial randomly assigned 7,112 noncardiac surgery patients at risk of perioperative cardiovascular events to 70% N2O or 70% N2 groups. The aim of this follow-up study was to determine the effect of nitrous oxide on a composite primary outcome of death and major cardiovascular events at 1 yr after surgery.MethodsOne-year follow-up was conducted via a medical record review and telephone interview. Disability was defined as a Katz index of independence in activities of daily living score less than 8. Adjusted odds ratios and hazard ratios were calculated as appropriate for primary and secondary outcomes.ResultsAmong 5,844 patients evaluated at 1 yr, 435 (7.4%) had died, 206 (3.5%) had disability, 514 (8.8%) had a fatal or nonfatal myocardial infarction, and 111 (1.9%) had a fatal or nonfatal stroke during the 1-yr follow-up period. Exposure to nitrous oxide did not increase the risk of the primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P = 0.27), disability or death (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P = 0.44), death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P = 0.10), myocardial infarction (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P = 0.78), or stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P = 0.70).ConclusionThese results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease.

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